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目的探讨二肽基肽酶Ⅳ(DPP4)抑制剂西格列汀、维格列汀、沙格列汀降糖作用的高低。方法采用高脂饲料喂养加ip小剂量链脲佐菌素建立Ⅱ型糖尿病大鼠模型。将大鼠随机分为对照组、模型组、西格列汀、维格列汀、沙格列汀组,Gly-Pro-AMC荧光底物法测定体内外DPP4抑制率,放免法测定血浆胰岛素浓度,ELISA测定血浆GLP-1浓度。结果西格列汀在体外抑制DPP4的活性高于维格列汀和沙格列汀。与模型组比较,DPP4抑制剂各组均能明显降低血糖水平(P<0.05),升高血浆胰岛素和GLP-1水平(P<0.05),改善胰岛素抵抗,沙格列汀在体内抑制DPP4活性及升高胰岛素和GLP-1水平优于西格列汀和维格列汀。结论沙格列汀降糖效能在3种抑制剂中效能最高,具有更好的经济性价比,为Ⅱ型糖尿病患者的治疗提供了新的药物选择。 相似文献
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Manoj Chawla Tae Ho Kim Roberto C. Mirasol Pathan Faruque Kathryn Cooke Peggy Hours-Zesiger 《Current medical research and opinion》2018,34(9):1605-1611
Aims: To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM).Methods: INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c)?≥?7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7.0%, change in body weight at 12 and 24 weeks, change in HbA1c by sub-groups (baseline HbA1c, age, body mass index [BMI], dosage strength, co-morbidities) from baseline to week 24, and safety.Results: A total of 532 patients were enrolled. The mean age, HbA1c, and BMI were 49.6?±?11.27 years, 9.3?±?1.57%, and 26.7?±?4.50?kg/m2, respectively. Cardiovascular risk factors present at baseline were dyslipidemia (30.1%), hypertension (29.7%), and obesity (20.9%). The mean reductions in HbA1c from baseline to week 12 (?1.6?±?1.59%) and 24 (?1.9?±?1.70%) were statistically significant (p?.001). At 24 weeks, 39.6% of patients achieved HbA1c?≤?7.0%, and the mean body weight reduction was ?1.1?±?2.62?kg. HbA1c reductions were consistently seen from baseline to weeks 12 and 24 in the various sub-groups. Overall, 48 (9.0%) patients reported adverse events, including one hypoglycemic episode. There were no serious adverse events or deaths.Conclusions: Overall, in a relatively young drug-naïve T2DM Asian study population with high baseline HbA1c and often associated with cardiovascular risk factors, vildagliptin/metformin combination therapy was associated with significant and clinically relevant HbA1c reduction from baseline. This effect was seen at week 12, was maintained over 24 weeks, and was accompanied by good tolerability. 相似文献
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目的:研究在接受胰岛素治疗的2型糖尿病患者中,联合应用维格列汀治疗的疗效及对胰岛素剂量的影响并进行安全性评价。方法:本实验为前瞻性、开放性、前后自身及空白对照的临床研究。设立试验组和对照组,试验组为110例应用胰岛素治疗的2型糖尿病患者,加用维格列汀50mg,每日2次,治疗12周,对照组为109例应用胰岛素治疗12周的患者,观察两组治疗前后糖化血红蛋白(HbA1c)及血糖变化。结果:治疗12周后,试验组HbA1c由基线的(9.27&#177;1.42)%降至(7.82&#177;1.36)%,下降了(1.45&#177;1.03)%,对照组HbA1c由基线的(8.86&#177;1.06)%降至(8.02&#177;1.32)%,下降了(0.84&#177;1.13)%,两组下降幅度均P&lt;0.05。以HbA1c≤6.5%和HbA1c≤7.0%为目标值,治疗后试验组达标率为16.36%和43.63%,较治疗前增加12.76%和33.63%;试验组胰岛素用量由基线的53.9IU/d降至41.2IU/d,剂量减少23.56%,对照组胰岛素用量由基线的66.7IU/d降至58.3IU/d,剂量减少12.59%,两组胰岛素减少量P&lt;0.05;患者空腹血糖及餐后2h血糖均有明显改善;患者平均每日药品费用较治疗前无明显增加(P&gt;0.05)。治疗期间试验组共14例患者(12.7%)发生一般性低血糖事件(24件&#183;次),无严重低血糖事件发生,与对照组比较,低血糖发生率有统计学差异(P&lt;0.05)。结论:维格列汀联合胰岛素治疗2型糖尿病,可有效降低患者空腹及餐后血糖水平,利于实现HbA1c达标,并减少胰岛素使用剂量,提高治疗的安全性及耐受性。 相似文献
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《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2022,16(3):102437
Background and aimsThis study aimed to assess the effects of vildagliptin on the prevention of cardiovascular diseases in Thai patients with type 2 diabetes mellitus using the Thai Cardiovascular Risk Score.MethodsAll patients with type 2 diabetes mellitus who used vildagliptin at a secondary hospital in Thailand were screened and recruited. The relevant variables were obtained from patient medication charts at the first visit on which the patients were prescribed vildagliptin and from the 6-month, 12-month, and 18-month post-treatment visits. The Thai Cardiovascular Risk Score was calculated and monitored as a primary outcome, whereas changes in separate cardiometabolic parameters were assessed as secondary outcomes.ResultsOf the 321 patients screened, only 95 were recruited for the analysis. The average 10-year cardiovascular risks of patients increased from 19.65% at baseline to 20.74%, 20.69%, and 23.78% at 6, 12, and 18 months post treatment, respectively. However, a better trend of reduction in cardiovascular risk was observed in patients with a high baseline cardiovascular risk. The glucose-lowering effects of vildagliptin were significantly observed 12 months of treatment onwards, but non-significant changes were found in lipid and blood pressure levels as well as body mass index.ConclusionVildagliptin provided a promising glucose-lowering effect in Thai patients with type 2 diabetes mellitus. However, the mean 10-year cardiovascular risk did not significantly decrease. However, a negative correlation between cardiovascular risk reduction and baseline cardiovascular risk was observed in this study. Low sample size was a major limitation of this study. 相似文献
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《Actas dermo-sifiliográficas》2020,111(3):249-253
BackgroundThe association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting.MethodsWe selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns.ResultsOf the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response.ConclusionsDPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment. 相似文献
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《Current medical research and opinion》2013,29(5):1131-1138
ABSTRACTObjective: Vildagliptin is a potent and selective dipeptidyl peptidase?IV (DPP?4) inhibitor that improves glycemic control in patients with type 2 diabetes by increasing alpha and beta-cell responsiveness to glucose. This study assessed the effect of multiple doses of vildagliptin 100?mg once daily on warfarin pharmacokinetics and pharmacodynamics following a single 25?mg oral dose of warfarin sodium.Research design and methods: Open-label, randomized, two-period, two-treatment crossover study in 16 healthy subjects.Results: The geometric mean ratios (co-administration vs. administration alone) and 90% confidence intervals (CIs) for the area under the plasma concentration-time curve (AUC) of vildagliptin, R- and S?warfarin were 1.04 (0.98, 1.11), 1.00 (0.95, 1.04) and 0.97 (0.93, 1.01), respectively. The 90% CI of the ratios for vildagliptin, R- and S?warfarin maximum plasma concentration (Cmax) were also within the equivalence range 0.80–1.25. Geometric mean ratios (co-administration vs. warfarin alone) of the maximum value and AUC for prothrombin time (PTmax, 1.00 [90% CI 0.97, 1.04]; AUCPT, 0.99 [0.97, 1.01]) and international normalized ratios (INRmax, 1.01 [0.98, 1.05]; AUCINR, 0.99 [0.97, 1.01]) were near unity with the 90% CI within the range 0.80–1.25. Vildagliptin was well tolerated alone or co-administered with warfarin; only one adverse event (upper respiratory tract infection in a subject receiving warfarin alone) was reported, which was judged not to be related to study medication.Conclusions: Co-administration of warfarin with vildagliptin did not alter the pharmacokinetics and pharmacodynamics of R- or S?warfarin. The pharmacokinetics of vildagliptin were not affected by warfarin. No dosage adjustment of either warfarin or vildagliptin is necessary when these drugs are co-medicated. 相似文献
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Shinji Kume Takashi Uzu Chieko Takagi Morihiro Kondo Tomoko Okabe Shin‐ichi Araki Keiji Isshiki Naoko Takeda Keiko Kondo Masakazu Haneda Daisuke Koya Yoshihiko Nishio Atsunori Kashiwagi Hiroshi Maegawa 《Journal of diabetes investigation.》2012,3(3):298-301
Anti‐diabetic agent‐related hypoglycemia is a serious complication in type 2 diabetic patients on hemodialysis. Therefore, we assessed the efficacy and tolerability of 24 weeks of monotherapy with vildagliptin, a dipeptidyl peptidase four inhibitor, which is a new class of antidiabetic agent. This open‐label, single‐arm clinical trial was performed on 26 patients on hemodialysis. The primary assessments were changes in postprandial glucose level and glycated albumin (GA). During the study, three patients dropped out, and data from 23 patients were analyzed. Significant reductions were seen in postprandial glucose (−2.60 ± 3.80 mmol/L, P < 0.001) and GA (−2.59 ± 2.33%, P < 0.001) levels. No serious drug‐related adverse events were observed. Vildagliptin monotherapy can be recommended for glycemic control in type 2 diabetic patients on hemodialysis. This trial was registered with the University Hospital Medical Information Network (no. UMIN000003661). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00169.x, 2011) 相似文献
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《Clinical therapeutics》2014,36(12):2072-2079
PurposeAlthough recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV (DPP-IV) inhibition contributes to heart failure in high-risk patients. The purpose of this research is to understand heart failure risk among high-risk patients with type 2 diabetes.MethodsThis is a systematic review of data published in full papers and abstract form using the terms DPP-IV inhibitors and heart failure published since October 2013. Data from insurance and hospital databases were combined with those from multiple published trials, including the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial; Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care (EXAMINE), and Vildagliptin in Ventricular Dysfunction Diabetes (VIVIDD) trial as well as pooled analyses of linagliptin and saxagliptin placebo-controlled trials to examine heart failure among patients represented in those datasets.FindingsA meta-analysis of the 9 datasets showed an increase in heart failure with dipeptidyl peptidase IV inhibitors of 15% (P = 0.017). There was no statistical heterogeneity, nor was there a statistical difference between cohort studies and randomized, controlled trials (P = 0.3), even though cohort studies alone were not significant (relative risk: 1.1; P = 0.32). Removing SAVOR-TIMI 53 data produced an insignificant increase in heart failure of 12% (P = 0.09) in the rest of the studies. In the randomized, controlled trials, the increased risk was 24% (P = 0.002). There was no statistical difference between those studies with and without baseline cardiovascular disease (P = 0.58), although the cardiovascular disease studies were borderline significant (P = 0.06). There was no publication bias.ImplicationsThere are data from studies using sitagliptin, saxagliptin, and alogliptin showing that these agents may increase the risk of hospitalization for heart failure. More data are required for a definitive conclusion. 相似文献
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